Barts-MS rose-tinted-odometer: ★★
In the last 2-3 years I have been talking about the need for the MS community to treat-2-target beyond NEDA (no evident disease activity) to try and prevent end-organ damage. Yes, we need to protect the end-organ in MS just as the nephrologists try to protect the kidney in autoimmune kidney disease and the rheumatologists the joints in rheumatoid arthritis (RA).
However, in a very similar way to MS if you let too much damage accumulate in the kidney or RA joint self-perpetuating mechanisms are set up that lead to slow deterioration in kidney and joint junction and they eventually fail. Fortunately for nephrologists, you can put patients with kidney failure on renal dialysis (an artificial kidney) or offer a kidney transplant (substitute kidney) and in RA you can replace the joints. In comparison, in MS you can buy walking sticks, walkers, wheelchairs and exoskeletons, but you can’t repair and restore lost neurological function. This is why the ‘diagnose early, treat early, treat effectively’ message is so important. Yes, time really is brain.
There is a longstanding theory that the biology of MS changes with time. So with time as the inflammatory infiltrates within the central nervous system increase, B-cell follicle-like structures develop, plasma cells take up residence, oligoclonal IgG bands appear and increase in number, microglia become diffusely activated, slowly expanding lesions or SELs increase in number, astrocytes get activated and form glial scars, demyelination increases, remyelination fails, axonal and cortical plasticity decrease and synaptic pruning increase the die is set and the course of MS becomes unmodifiable with our current DMTs. In essence ‘smouldering MS’ becomes the real MS and we can’t modify it.
In the Queen Square longitudinal CIS study (see below) the EDSS score at 14 years correlated with the lesion volume on MRI at 5 years and the increase in lesion volume over the first 5 years. In the London Ontario natural history study it was the number of relapses in the first two years that predicted poor outcome. So pwMS who only had 1 relapse in the first 2 years compared to those who had 3 or more relapses took 7.6, 12.8 and 20.3 years longer to reach EDSS scores 6 (walking stick), 8 (bed) and 10 (death), respectively. Also, subjects who developed early disability, i.e. EDSS 3.0, become disabled quicker, i.e. they reached higher EDSS scores much quicker than those who don’t develop early disability. In other words, disability begets disability.
Therefore the clinical philosophy of watchful-waiting is hardly practised anymore even in patient’s who are diagnosed with clinically isolated syndrome (CIS). If patients with CIS have high-risk scans, i.e. lesions on the scan that look like demyelinating lesions, most neurologists now feel obliged to offer these patients treatment. A big debate now is how aggressively do you treat people with CIS. Do you simply start them on a safe platform therapy? Or do you hit their disease with a potent IRT? I would argue the latter but instead of using alemtuzumab or HSCT, I would recommend something like oral cladribine. However, this is not possible, cladribine is not licensed for CIS and the current NHS England treatment algorithm is quite clear that we shouldn’t treat CIS.
Treatment Algorithm for Multiple Sclerosis Disease-Modifying Therapies (NHS England Reference: 170079ALG, Date Published: 4 September 2018, Updated: 8 March 2019 Gateway reference: 07603)
‘Trials of first-line therapies in people with the original definition of Clinically Isolated Syndrome (CIS) at high risk of conversion have NOT shown a convincing long-term effect on the accumulation of disability. In 2018, NICE concluded that it was “unable to make recommendations for treating clinically isolated syndrome because the diagnostic criteria for multiple sclerosis and clinically isolated syndrome have changed and the treatment pathway has evolved”. These new diagnostic criteria are the 2010 and 2017 McDonald criteria.’
Fortunately, the number of patients presenting with a clinical event who have CIS is now very small and most of them have MS after underground a lumbar puncture and are shown to have CSF OCBs or convert to becoming MS very quickly. The question for pwCIS is how much damage will occur in the time window between presentation with CIS and conversion to MS and is this watchful waiting period of time long enough to allow the biology of MS to change, i.e. for smoulder MS pathology to take up residence in the CNS?
The question therefore remains is how early is early when it comes to treating MS? I would argue as early as possible, which is why when we were approached to be a trial centre to assess a very high efficacy DMT in RIS (radiologically isolated syndrome) or asymptomatic MS we said yes.
I would be interested to know how many of you who had been diagnosed with CIS were treated immediately, how many of you were asked to watchfully wait before being offered treatment and how many of you still have CIS?
Brex et al. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002 Jan 17;346(3):158-64. doi: 10.1056/NEJMoa011341.
Background: In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability.
Methods: Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke’s Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability).
Results: Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61).
Conclusions: In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.
Scalfari et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010 Jul;133(Pt 7):1914-29.
The relationship of relapses to long-term disability in multiple sclerosis is uncertain. Relapse reduction is a common therapeutic target but clinical trials have shown dissociation between relapse suppression and disability accumulation. We investigated relationships between relapses and disability progression for outcomes of requiring assistance to walk, being bedridden and dying from multiple sclerosis [Disability Status Scale 6, 8, 10] by analysing 28 000 patient-years of evolution in 806-bout onset patients from the London Ontario natural history cohort. Having previously shown no effect of relapse frequency among progressive multiple sclerosis subtypes, here we examined these measures in the pre-progressive or relapsing-remitting phase. Survival was compared among groups stratified by (i) early relapses–number of attacks during the first 2 years of multiple sclerosis; (ii) length of first inter-attack interval; (iii) interval between onset and Disability Status Scale 3 (moderate disability); (iv) number of attacks from the third year of disease up to onset of progression; and (v) during the entire relapsing-remitting phase. Early clinical features can predict hard disability outcomes. Frequent relapses in the first 2 years and shorter first inter-attack intervals predicted shorter times to reach hard disability endpoints. Attack frequencies, in the first 2 years, of 1 versus >or=3, gave differences of 7.6, 12.8 and 20.3 years in times from disease onset to Disability Status Scale 6, 8 and 10, respectively. Time to Disability Status Scale 3 highly and independently predicted time to Disability Status Scale 6, 8 and 10. In contrast, neither total number of relapsing-remitting phase attacks nor of relapses experienced during the relapsing-remitting phase after the second year up to onset of progression showed a deleterious effect on times from disease onset, from progression onset and from Disability Status Scale 3 to these hard endpoints. The failure of a regulatory mechanism tied to neurodegeneration is suggested. Relapse frequency beyond Year 2 does not appear to predict the key outcome of secondary progression or times to Disability Status Scale 6, 8 or 10, highlighting two distinct disease phases related to late outcome. These appear to be separated by a watershed within the relapsing-remitting phase, just a few years after clinical onset. Higher early relapse frequencies and shorter first inter-attack intervals herald more rapid deterioration via interaction with the neurodegeneration characterizing secondary progression. They increase the probability of its occurrence, its latency and influence–to a lesser degree–its slope. The prevention or delay of the progressive phase of the disease is implicated as a key therapeutic target in relapsing-remitting patients.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
I work in neurology, I won’t say my grade or location but what I will say is that had I not been in the profession I was in would I been diagnosed? Probably not. Would I be on treatment – even less likely. Would I be on Ocrevus – almost impossible.
So much about life and healthcare outcomes in particular are down to fortune and luck of where one lives and the neurologist you see. It’s a shame that healthcare is such a lottery.
Till we make the management of MS and so many other neurological disorders more objective based on quantifiable bio markers that then that will sadly not change.
We need more policies for the standardization of care
Agree, it helped me get into A & E and heart opperation, yes I blogged whilst in hosptal…thank god for Euduroam (the hosptial network was pants but eudroam is a separate univeristy network that gives internet access to any university person in any university associated building anywhere in the world. Sadly A&E was a internet and mobile phone dead zone luckily NDG found me in A & E 6 hours after admission to inform Ms Mouse)…probably would have had stroke or heart attack whilst waiting two weeks to see a GP. At least with home blood pressure monitoring I knew there was something seriously wrong which was confirmed by Neurology ECG. I guess we cant put an MRI in the garage but maybe if we could do remote neurofilament monitoring
Mouse this sounds awful! I hope you are recovering ok from this? Sending you best wishes
Thanks I am guessing this best wishes relates to the heart issue…rather than the metaphorical snip:-). The major heart issues and trip to the Royal London was a few years ago…..but suspect my blood pressure is not great now:-)…..If I told you the back story about that issue then you really would think it was awful….at least I didnt have the stroke. However, what happened in WhiteChapel stays in whitechapel:-)
We dont make a song and dance about it and its not about our woes. We all have health issues some worse than others, during the blog years MD2 has also been knocking on death’s door. I went to see him in Hosptial took him a lad mag ..yep a copy of “Guitarist”….MD2 is partial to abit of Guitar-porn, but looking at those pictures of Fender stratocasters and Gibson Less Pauls etc. can’t have been good as after I left his blood saturations dropped to over 80% on 20litres/minute of oxygen and he didnt even have COVID. (P.S. Anything below 95% without oxygen sends alarm bells)….but luckily Dr.House came along and sorted out his diagnosis….and he didnt even need an brain biospy, MRI which Dr.House seems to always do.
We all have health issues some more devastating than others….but it not about ours:
But thanks for the best wishes
Well I am glad you survived to tell the tail!
And the snip! Still putting off getting my dog the chop, he seems to like his balls 🙁
Maybe Tedno will find something else to lick 🙂 Tedno = Ted with no nads:-)
Gosh, do get better quickly.
Caneco
Thats why you went to do mri a couple months back?
Are you ok ?
Taking medicine?
Im OK, the MRI was for something different related to my back….for the former was on anti-coaggulants and other heart medications, the surgery has worked well.
I was treated with alemtuzumab, off license, on first attack back in 2011. It was a whopper of an attack, totally paralyzed from chest down. I didn’t really know what MS was back then & was shocked by the strength of alemtuzumab once I returned home & had time to read up on things.
I experienced a very small relapse approximately 6 years ago.
I do sometimes wonder how things would have turned out if I had been treated differently. As it is I am mobile unaided, in the same employment as I was before & most importantly, I now have two grown up children at university who, I think, haven’t really had their upbringing effected by their mother’s illness very much. I still have some residual problems from the first event such as a numb left leg, however I am deeply grateful to that first forward thanking neurologist who treated me back then. Sadly he emigrated to Australia not long afterwards.
Now, aged 53, I do worry about smouldering MS. My current neurologist doesn’t really answer these concerns when I try to discuss them. I have only had one MRI since I was first diagnosed at the time of the relapse, though that confirmed that original lesions in brain & spine were inactive. The last couple of years I have experienced problems with ITP though medical teams feel this is more likely due to an over active immune system rather than the alemtuzumab.
But coming back to your article & should we treat at CIS? I think it would be cruel not to.
“ITP though medical teams feel this is more likely due to an over active immune system rather than the alemtuzumab.”
It occurs after hsct so probably related to alemtuzumab.
The ITP started a week after the flu vaccine 2 years ago. The local haemotology team laughed & said they see this most years in flu vaccine season. Deep down I still think it’s alemtuzumab related, but it’s impossible to prove. My neurologist wouldn’t / couldn’t commit.
It seemed to sort itself out, but reared it’s head again 6 months ago. Still can’t get the platelet level stable.
I don’t get how, there can be a delay on treatment, personally I had a 7 month wait to get a treatment. Why it took that long I have no idea. It’s like there no urgency. I mean if you cut your arm you get a bandage. Have a brain illness and theres a big wait.
Surely other disease treatments don’t start on a lower efficacy drug and hope for the best, I may be wrong?
It’s great MS has some life changing treatments especially for RRMS and hopefully PPMS and SPMS soon. But they have to be used.
So many thoughts. My diagnosis took 12 years, 3rd episode was the charm. Gadolinium lit up my C 5 lesion and I was on my way. 2008. Now I question the use of Gadolinium, feeling I have retained it, but that’s a different battle.
I believe All CIS Clinically Isolated, First timers should get Something besides a Whew, we haven’t found anything. I really thought left sided numbness was just something I had now. Optic Neuritis next. Oh, Neuro Opthomologist peered at my nerve, gave me a round of sight saving High Dose Steroids and 2 years later my Right side went numb. But that’s ancient history. 1980’s.
I wanted to come here and tell you why you should defy NHS like doctors here in USA can.
Will tweet you a few screenshots. You have One Master Health Decision Maker. We, in USA have several. Also the Drug companies have copay assistance. I don’t know if Clabridine is approved for CIS by insurance companies but I suspect maybe not.
The drug company has copay assistance. ? For CIS?
Medicaid looks to have criteria like yours-not for CIS.
I would rather have been treated the 12 years waiting for diagnosis, if the culprit was my genetics plus bad EBV infection at age 19. I started treatment 30 years later.
US label the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease.
My sister was told she had CIS,70/ 80% chance of developing MS in the next 5 years I think it was? She wasn’t given additional MRIs etc. No follow up. I don’t think it was in the guidelines at that point (around 4 years ago now). She was diagnosed with MS after I was – because she sought out private neurology appointment and another MRI. Seemed pretty likely she had it if I did! She actually ended up having a second relapse around that time too with optic neuritis in both eyes. She was then diagnosed with that and the MRI. She was told her MS was acting mild, but about a month after that it didn’t seem mild! Just shows how quickly things can change. Saying that her last MRI is now stable on Tecfidera. If I hadn’t been diagnosed her diagnosis would have been slower, though I guess she would have gotten it when she had the 2nd ON bout probably pretty quickly.. seems similar to most people’s stories. My first episode wasn’t even suspected MS so no way to even be diagnosed as CIS – also common I imagine
My first symptom of MS was optic neuritis (24ish years ago), which I guess classes as CIS. I was told it might be an isolated event and received no treatment at all. It cleared up in 3 months. I then was diagnosed with RRMS 2 or 3 years later when I developed new symptoms. I believe I had a lumbar puncture when I had the optic neuritis. I gave up nursing due to the MS. I wonder if I had been treated earlier if I would still be able to work. Just a rumination.
First episode 1 of february 2016
Abnormal mri 13 of april 2016
Diagnosed june 2016
Hsct november 2017
Last mri 5 pf january 2021
Normal
My neuro doc (whic i like very much) said : dont do it you gonna die ,etc
Great! Do you live in the UK?
No
Suffered an attack of optic neuritis, mri at time abnormal. Had to push to see a specialist neuro as the general neuro thought it was insignificant – quote mris show up the slightest thing these days. The ms specialist neuro classed me as CIS, arranged folllow up mri and lumber 6 months later which showed a lesion enhancing upon contrast and positive OCB but didn’t receive MS diagnosis until a further 6 months time ( which was 15 months after the ON) – asked to have treatment but told no – then a year later after that got offered Tecfidera- nothing had changed over the last year but I grabbed treatment. From speaking to others I don’t think my experience is that unusual.
Mildly numb leg 10yrs ago fully resolved (GP not interested)
3 months later ‘funny vision’ which turned out to be internuclear ophthalmoplegia diagnosed in eye casualty.
Neurologist – completely normal MRI. Convinced obviously by presentation so ordered LP – confirmed MS.
However was told mild as normal MRI so no treatment needed.
I actually went 8 years without a single episode or relapse.
Relapse (mild) in spinal cord and self limiting. But this one led to DMT (ocrelizumab)
I’m back at completely normal baseline again now with no residual symptoms. Would having a DMT over those 8 years have made a difference? I always thought not but this blog makes me think yes.
I was given a CIS diagnosis following a lesion at T5 in 2015. Brain scan also reported lesions but classified as non-specific. It was a struggle to even get to that stage as the my NHS nuero refused the referral. I went to A and E once, GPs at least twice….kept getting turned away. Ended up getting scanned and seen privately so at that stage I felt like I had pushed matters and was quite happy with the CIS diagnosis and the nuero’s relaxed attitude….sort of forgot about it for 4 years. Then episode 2….still had a 9 month delay before treatment due to covid delays, another relapse in between which has left me with persistent symptoms even though I’m fully mobile. I do blame myself a bit for not pushing harder in 2015 when I think other neuros may have actually diagnosed it as MS or at least pursued a lumbar puncture. Alemtuzumab was available then….my reserve was higher. However, it wasn’t like I was sitting still. I spent 000s even getting to the point that people would listen, when I received ‘positive’ news from the nuerologist….I trusted him. I have heard many worse stories than my own and still find it unbelievable how much reliance is placed on the patient being their own advocate in MS. CIS just feels like another way of pushing things down the road for the treating nuerologist….off the desk, on to the next one. I don’t know how many patients are diagnosed a week in the UK or it’s regions but the importance or treating early in MS should mean that greater importance is placed on the diagnostic process….an expert panel? A critical friend / second opinion. Too many lives ruined by the postcode lottery in my view
Had my first MRI in 2011, after experiencing daily headaches and a general uneasy feeling. MRI showed possible MS, but no treatment or further testing was offered. Doctors said there was not enough evidence. Clearly it was CIS!!!
I was not diagnosed until 2018, after experiencing full left paralysis, Optic neuritis, and severe TN……2018 MRI showed several brain and cervical lesions!!
So yes, time is brain, and unfortunately by the time I was offer an effective DMT it was too late to stop….the train had already left the station.
Now the bigger question…..would I have taken a DMT, if offered one in 2011? Probably not at first, given the risk reward assessment I would have performed at that time. My point is that we not only have to educate neuros about DMT use at first signs of CIS/MS, we also need to do a better job educating patients about the long term risks of not acting at the first sign of MS/CIS:
Every newly diagnosed pwms should be required to read this blog as a standard of care. Perspective is sometimes the best motivation.
“Now the bigger question…..would I have taken a DMT, if offered one in 2011?”
that was my thought too with this post. I don’t think my sister would have taken one when she was diagnosed as CIS – unless given the risk / benefit conversation fully. She said she preferred to ignore she ‘might have MS’ after the CIS diagnosis. Probably a lot of people feel like that.
If my first episode had been told to me as MS/CIS – would i? I don’t know… Like you, only discovering this blog made me more educated, i think im not the kind of person who doesnt want to do ‘nothing’ so like to think i would have said yes… but you just dont know! Defo need the patients to be educated
She said she preferred to ignore she ‘might have MS’ after the CIS diagnosis. Probably a lot of people feel like that.
Well i was tottaly the oposite
I didnt rest until i have a diagnosed
And them i didnt rest after and everyday
I think the severity of the presentation can make a difference….both for the patient and the nuero. For many, the first episode has resolved itself by the time you get to see somebody. For others, a scarier and more sever presentation means that they cannot rest, they are taken through the diagnostic process in a and e and therefore things happen much quicker
I am more like you
Need to know, and have to be doing something.
I had no idea my first attack was MS though, so in a way had the luxury (or not) to live ignorant to the fact for 2.5 years.
If I didn’t find this blog though, I have no idea if I’d agree to take something that seems at first, really hardcore (now, I don’t feel that way at all about the MS drugs, but when I first looked into DMTs I was so scared, like many of us) at first attack without actual full diagnosis.
I think like the below person said, severity of attack (or your anxiety around ms as a disease/maybe knowing someone who’s had it badly) is going to make a big difference to your openness to take something at CIS.
I think the only way to get people to agree to the trial if they are anxious about drugs… is possibly for them to talk to other patients on the drugs who’ve had good experiences… I mean what are the real risks to taking a DMt and then being that small percent who doesn’t convert to MS? Is it that bad? Then again how would you know if they were effective??
Trust me, I fought every day for 7 years to find some compassion and find a doctor that would look past my generally healthy exterior.
I got a second, third, fourth, and fifth opinion! It was not until I was f@#king paralyzed, blind, and in excruciating pain, then they listened to me! Full spinal MRI and LP confirmed what I knew for the past ten years, I had MS.
Living in the U.S. and being a disabled veteran I expected better. And yes all of the “expert” medical opinions were from private doctors, not military. MS happened years after I was medically discharged with cancer. Been in remission for 15yrs 👍
Life is definitely more challenging for some. Nonetheless, I am happy to still be alive…..In a lot of pain and not able to achieve my full potential, but still alive 😉
So the question I have is how get people ready for ATTACKMS. This is a trial that aims to offer people with their first demyelinating treatment the option of treatment. The aim is to ensure there is not more disease activity. However, I imagine it is alot to take so how best should be explain this?
Neuros have to be willing to hold a 2 way conversation. Explain to the patient what they are dealing with and answer questions, failure to do that may raise suspicion and create mistrust. Some patients may need reassurance that they will be sufficiently monitored before committing to treatment.
Different scenario but it would have made all the difference to me, before it was too late. Good luck recruiting, I hope patients get what they need and in good time.
The good thing about ATTACK-MS is that natalizumab is very safe in the short-term and it is reversible in its mode of action, i.e. it doesn’t change the immune system and is not associated with any long-term effects. It is the ideal drug for the short-term control of MS. It is the ultimate short-term anti-inflammatory therapy for MS.
Simple
Make them talk with more advance patients
On the day you go into hospital and then someone says you may have MS and the next thing you have to see is someone with significant disability and have to make a choice it would be terrifying I imagine. However, is this what you would have wanted, I am sure it would be too much to take in.
“Make them talk with more advance patients”
Not ethical to use patients like that..but some
patients do it themselves on FB groups
“In 2010 I underwent a CCVSI operation in Belgium. That temporarily gave me relief, but unfortunately the decline continued. The progress of the MS really worried me and I worked on my recovery by exercising to build up some physical condition.
In January 2017, my Australian family gave me the idea to undergo an HSCT treatment. They told me that living with MS was not an option for the long run. At that time I had not yet seen MS patients in an advanced stage, but they had, and they said I would not be able to live with this disease.
From that moment on, I was looking out where HSCT was done and how the doctors did it. “
I dont think it will be difficult to convince patients, the majority anyway. Once someone tells you that there is something wrong with your brain or spinal cord, the next thing you want them to explain is what they are going to do about it. Whats the plan? How will you fix me. Just as you go to the doctors and generally come back with a cream or some pills…..this is just the natural and logical process for patients. Yes, MS treatments and tysabri are more severe but as long as a nuero explains the reasons, that it is reversible and is a preventative measure then my expectation is that most patients would jump at the chance. Probably best not to dwell on PML risk which could be scary
Good point MD. On one of my first visits to the ms clinic there was a young lady in a wheelchair. Her legs kept flinging up into the air almost pulling her out of it, it was a violent and noisy scene. The woman pushing the wheelchair said ‘Well this is just how it is now, you’ll just have to get used to it’. That was an eyeopener I would rather not have seen.
I had double vision and numbness on one side in 2013, aged 56. Diagnosed with MS. Vision cleared up pretty quick but numbness/pulling persists and, though variable, not much worse overall. Have been ‘signed off’. Read with interest (and concern) about smouldering MS and wonder if my MS will come to hit me badly at some point. Maybe we also need to advocate continued monitoring of people with CIS or like me – even if we don’t immediately treat, at least do more of the watching rather than simply waiting?
Are you sure there is such a thing as watchful waiting in neurology?
This is the Wikipedia definition: Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed.
https://en.wikipedia.org/wiki/Watchful_waiting
but if you aren’t presenting with any new bad stuff, would they be doing repeated testing?
Why is cladribine your IRT of choice for CIS?
Although one could give the pros and cons of cladribine….there is data (ORACLE) with cladribine, I think there is no data for alemtuzumab and no data for orcelizumab if you believe it is an IRT..many don’t. If only two phase III had been done to counter the adverse data…the treatment landscape could I suspect have been very different.
Fair comment. I ignored MS for as long as I could after diagnosis. I didn’t want to read anything or believe I would get any worse.
In order to calculate therapeutic lag, the researchers drew graphs to compare rates of relapses or disability progression in the years immediately before and after starting therapy. This revealed some notable trends. For example, there generally was a peak in relapses or disability progression right before treatments were started.
AANAM research focusing on measuring therapeutic lag.
Whatever the reason: watchful waiting, simply waiting on treatment to begin, use of the escalation model, misdiagnosis etc, etc, it’s abundantly evident that PwMS have accrued significant damage whilst still treatment naive.
Defining ‘early’ is profoundly difficult in these circumstances and I only wish it could become much closer to your definition of ‘early’ ProfG, and most importantly added to flipping the pyramid.
WAW sounds like wawful… I had a clear episode back in 2008 half body numb from the shoulder to the toe. Spent months to get MRI that found 3 brain lesions. No diagnosis not told I was a CIS. Watchful Waiting consisted in… just waiting. I did not do a proper MRI not before 11 years after the maybe next relapse. They found about 30 lesions. Now did I have asymptomatic lesions over 11 years or I had just one bad relapse in terms of lesions? I think neuro decided for the latter put me on ocrevus (not fit for tysabri) because of highly aggressive MS… some months later with only some eye issues left I was told my MS is benign. But I understood this is based on disability… that is my MS is benign because I was lucky about where the brain took the hits… looks like roulette and not encouraging. So, I think CIS must be treated. Just a few months ago while doing infusion the prof jumps in and tells a story that if he sees someone with CIS and he is sure it is a CIS in MS terms then he treats immediately. Things have changed
Caneco
My son, first attack 2010, optic neuritis, lumbar puncture revealed OCB’s, told to practice ‘watchful waiting’ for the next four years, a continued steady decline with him landing in hospital another three times for suspected relapses, eventually approved for rebif in 2014, he continued decline, we repeatedly requested but were refused more effective treatment (apparently the risk of those treatments outweighed the benefit – inspite of the fact that by now had lost the ability to continue his masters studies), instead our neurologist chose to put him onto another equally ineffective first level drug. We eventually changed neurologists, after two huge relapses he was approved for HSCT which we self funded for in 2018. He has lasting damage and now breakthrough disease post Hsct. I believe it is criminal to not at least offer patients (or to deny them as in my son’s case) the choice of effective treatment early on.
CIS+ OCB+, yes to treatment. I agree with IRT Cladribine, I totally disagree with Tysabri. The first can have the possibility to really alter early the course of the disease, the second will just hide it.
Another option for CIS patients could be Minocycline (+ hydrocholoquine)
https://www.nejm.org/doi/full/10.1056/NEJMoa1608889
https://mssociety.ca/library/document/xeiTEquHzgDKlmwV4Lav3dAph0rX1Pft/original.pdf
https://pubmed.ncbi.nlm.nih.gov/28857721/
https://www.researchgate.net/publication/8210631_Minocycline_inhibits_antigen_processing_for_presentation_to_human_T_cells_Additive_inhibition_with_chloroquine_at_therapeutic_concentrations
https://www.jns-journal.com/article/S0022-510X(15)02021-3/abstract
https://patentscope.wipo.int/search/zh/detail.jsf?docId=WO2018076107&tab=PCTBIBLIO
Another thing we should see is how many CIS OCB- actually have actually viral and post viral neurological manifestations (thank you Covid for highlighting something that was already happening).